title: Toxoplasma gondii protects against H(2)O(2) -induced apoptosis in ARPE-19 cells through the transcriptional regulation of apoptotic elements and downregulation of the p38 MAPK pathway.
abstract: OBJECTIVE
  Toxoplasmosis, which is caused by the protozoan parasite Toxoplasma gondii, can lead to severe visual impairment. T. gondii inhibits or delays programmed cell death caused by various apoptotic triggers; however, the mechanisms involved in the T. gondii-induced suppression of apoptosis in retinal cells have not been analysed in detail.
  
  
  METHODS
  We investigated the role of T. gondii infection in H(2)O(2) -induced apoptosis in human retinal pigment epithelial cells (ARPE-19) by monitoring the activities of apoptosis-regulating molecules and mitogen-activated protein kinases (MAPKs), including p38 MAPK. We also examined the gene downstream from p38 MAPK.
  
  
  RESULTS
  T. gondii infection significantly inhibited the cellular toxicity of H(2)O(2) (500 μm) and increased cell viability in a multiplicity of infection (MOI)-dependent manner by reducing DNA fragmentation and reactive oxygen species (ROS) generation in ARPE-19 cells. Western blot analysis also showed that T. gondii infection prevented the host cell expression of pro-apoptotic factors, such as Bad and Bax, and the activation of caspase-3. Infection with T. gondii increased the expression of the anti-apoptotic factor Bcl-2 in ARPE-19 cells under oxidative stress. In accordance with these findings, Toxoplasma infection was protective enough to suppress the phosphorylation of p38 MAPK following H(2)O(2) treatment. Exposure to H(2)O(2) increased the expression of heme oxygenase-1 (HO-1) in ARPE-19 cells, and its expression was significantly inhibited in H(2)O(2) -treated infected cells.
  
  
  CONCLUSIONS
  The protective function of T. gondii infection against ROS-induced apoptosis results from changes in the expression of apoptotic molecules and the downregulation of stress-induced intracellular signalling.
authors.affiliation: Department of Ophthalmology, Chungnam National University School of Medicine, Daejeon, Korea.
authors.forename: Si-Hwan
authors.initials: SH
authors.lastname: Choi
authors.forename: Sung Jun
authors.initials: SJ
authors.lastname: Park
authors.forename: Guang-Ho
authors.initials: GH
authors.lastname: Cha
authors.forename: Juan Hua
authors.initials: JH
authors.lastname: Quan
authors.forename: Nam-Sik
authors.initials: NS
authors.lastname: Chang
authors.forename: Myoung-Hee
authors.initials: MH
authors.lastname: Ahn
authors.forename: Dae-Whan
authors.initials: DW
authors.lastname: Shin
authors.forename: Young-Ha
authors.initials: YH
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival; D053938:DNA Fragmentation / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism / Q000469:parasitology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014122:Toxoplasma / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases